Transgenic mouse models have been invaluable for the study of cancer pathogenesis as well as immune system function. In our initial SPORE application, we proposed to produce two categories of prostate specific transgenic mice. One category involved the introduction of oncogenes under a prostate specific androgen regulated promoter and the other category consisted of introducing model antigens into prostate specific transgenics. In particular, we have chosen model antigens against which we have obtained T cell receptor transgenic mice. These mice contain large numbers of T cells expressing the transgenic T cell receptor against the model antigen. The purpose of these projects is to study the mechanisms by which the immune system normally tolerates prostate specific and prostate cancer antigens and to explore specific strategies to break that tolerance with therapeutic intent. We have successfully produced transgenic mice expressing the influenza hemagglutinin gene product under control of both the C3 and probacin promoters. We have initiated a collaboration with Dr. Norman Greenberg and colleagues of the Baylor SPORE, who have successfully produced and begun to characterize prostate specific oncogene transgenic mice that develop prostate cancer. By mating these animals together, and analyzing immune responses against these model antigens when both are mechanisms for T cell tolerance as well as immunotherapy strategies to break tolerance and treat prostate cancer expressing prostate specific antigens. Specifically, we plan to 1) characterize a number of prostate specific transgenic mice expressing model antigens against which we have obtained T cell receptor transgenic mice. 2) introduce the transgenic T cells into the prostate specific transgenic mice to determine the nature of the response of these specific T cells. 3) mate these animals to the oncogene transgenic mice produced by Dr. Greenberg and study changes in the immune response when prostate cancer is expressing these antigens develop. 4) explore antigen specific gene therapy and vaccine strategies for the treatment of these prostate cancers.